3-Anilino-5,5-disubstituted-2-aminomethyl-2-cyclohexen-1-ones and the salts thereof

ABSTRACT

Novel cyclohexenone derivatives, which are shown by the general formula ##SPC1## 
     Wherein each of R 1  and R 2  represents a hydrogen atom, lower alkyl or phenyl group; one of R 3  and R 4  represents a hydrogen atom or lower alkyl group, and the other represents an unsubstituted or substituted phenyl, lower alkyl or aralkyl group, or R 3  and R 4 , taken together with the adjacent nitrogen atom, form a 5 to 6-membered heterocyclic ring; one of R 5  and R 6  represents a hydrogen atom or lower alkyl group, and the other represents a lower alkyl, phenyl or aralkyl group, or R 5  and R 6 , taken together with the adjacent nitrogen atom, form an unsubstituted or substituted 5 to 6-membered heterocyclic ring, and their pharmaceutically acceptable salts, useful medicines such as analgesics.

The present invention relates to novel cyclohexenone derivatives havinguseful pharmacological actions such as analgesic action, which are shownby the general formula (I) ##SPC2##

wherein each of R¹ and R² represents a hydrogen atom, lower alkyl orphenyl group; one of R³ and R⁴ represents a hydrogen atom or lower alkylgroup, and the other represents an unsubstituted or substituted phenyl,lower alkyl or aralkyl group, or R³ and R⁴, taken together with theadjacent nitrogen atom, form a 5 to 6-membered heterocyclic ring; one ofR⁵ and R⁶ represents a hydrogen atom or lower alkyl group, and the otherrepresents a lower alkyl, phenyl or aralkyl group, or R⁵ and R⁶, takentogether with the adjacent nitrogen atom, form an unsubstituted orsubstituted 5 to 6-membered heterocyclic ring, and theirpharmaceutically acceptable salts.

The present invention relates also to a process for the production ofthese cyclohexenone derivatives.

Hitherto, there have been many kinds of analgesics, and some of themhave been put into practical use. However, aforesaid analgesics are notsatisfactory in view of some drawbacks such as showing rather weakanalgesic action.

Under these circumstances, the present inventors have made extensivestudies and succeeded in synthesizing novel cyclohexenone derivatives(I) defined above. And the present inventors have also unexpectedlyfound that these compounds have an analgesic action as well as, forexample, sedative, tranquilizing, antipyretic, anticonvulsive andantitussive actions in mammals, and moreover that these compounds havean action to depress blood sugar level in mammals.

The present invention has been accomplished on the basis of thesefindings.

Thus, the principal object of the present invention is to provide thecyclohexenone derivatives (I) and their pharmaceutically acceptablesalts useful as analgesics, sedatives, tranquilizer, antipyretics,anticonvulsant, antitussives and drugs for treatment of diabetes, andanother object of the present invention is to provide a method for theproduction of these compounds.

In general formula (I), the lower alkyl group represented by the symbolsR¹ to R⁶ respectively may be any of saturated, unsaturated, straight,branched or cyclic ones having 1 to 6 carbon atoms. Typical examples ofthe saturated, unsaturated, straight or branched alkyl group may bemethyl, ethyl, propyl, isopropyl, allyl, 1-propenyl, butyl, isobutyl,sec-butyl, tert-butyl, pentyl or hexyl group, and typical examples ofthe cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl orcyclohexyl group. Among these alkyl groups, a lower alkyl group of about1 to 4 carbon atoms is preferable from the practical point of view.

The aralkyl group represented by the symbols R³ to R⁶ respectively may,for example, be benzyl or phenethyl group. The 5 to 6-memberedheterocyclic ring which is formed by R³ and R⁴ or by R⁵ and R⁶, as theyare taken together with the corresponding adjacent nitrogen atom, may bethat containing 1 to 2 hetero atoms (e.g. oxygen atom and nitrogenatom), such as pyrrolidino, morpholino, piperazino, piperidino and soforth.

When the phenyl group represented by the symbol R³ or R⁴ and/or the 5 to6-membered heterocyclic ring formed by R⁵ and R⁶ are substituted, thesubstituents of these phenyl and/or heterocyclic ring are exemplified bylower alkyl groups having 1 to 3 carbon atoms, which may have hydroxylgroups(s), (e.g. methyl, hydroxymethyl, ethyl, 2-hydroxyethyl, propyl,isopropyl, 3-hydroxypropyl, etc.), lower alkoxy groups having 1 to 3carbon atoms (e.g. methoxy, ethoxy, propoxy, isopropoxy, etc.), halogenatoms (chlorine, bromine, iodine and fluorine), nitro, hydroxyl, mono-or di- lower alkyl substituted amino groups whose alkyl moiety is thathaving 1 to 2 carbon atoms (e.g. dimethylamino, diethylamino,methylamino, ethylamino, etc.), lower acylamino groups whose alkylmoiety is that having 1 to 2 carbon atoms (e.g. acetylamino,propionylamino, etc.) and so forth. These substituents may occur in anyoptional number, preferably 1 or 2 and in any optional positions on thephenyl and/or heterocyclic ring.

In the present invention, the object compounds (I) are produced by theprocess described below: ##SPC3##

wherein R¹ to R⁶ are as defined above.

The process of Step (A) is carried out by reacting a dione compound(III) with an amine compound (IV). The amount of the compound (IV) isone or more moles per mole of the compound (III), and there ispractically no upper limit thereof. However, it is usually desirable toemploy about 1 to about 3 moles and, more preferably, about 1 to about1.5 mole of the compound (IV) per mole of the compound (III). Thereaction of this step (Step (A)) is ordinarily conducted in a solvent,and as the solvent, any one may be employed if it is not detrimental tothe reaction. As these solvents, there may, for example, be water,aliphatic hydrocarbons or halogenated aliphatic hydrocarbons (e.g.pentane, hexane, cyclohexane, dichloromethane, dichloroethane,chloroform, carbon tetrachloride, etc.), aromatic hydrocarbons (e.g.benzene, toluene, xylene, nitrobenzene, etc.), ethers (e.g. ethyl ether,tetrahydrofuran, isopropyl ether, dioxane, etc.), alcohols (e.g.methanol, ethanol, propanol, isopropanol, butanol, etc.),dimethylformamide and the like. The reaction may also be conducted inthe absence of a solvent by using an excess amount of the compound (IV),because the excess of the compound (IV) acts as the reaction solvent inthis step. While the reaction conditions such as temperature and timeare not critical, it is generally advisable to conduct the reaction at atemperature near the boiling point of the reaction solvent used or ofthe amine compound (IV) for about 0.5 to about 2 hours. But, ifnecessary one may conduct the reaction at temperatures higher than orbelow the boiling point of the solvent used or the amine compound (IV)for an extended period of time. Moreover, while the reaction of thisstep can be conducted by merely allowing the compound (III) to contactwith the compound (IV), the reaction may be accelerated and conductedmore smoothly by employing a suitable condensing agent such as anhydrouspotassium carbonate, anhydrous sodium carbonate, p-toluenesulfonic acid,calcium chloride or acetic acid or, alternatively, or employing anaromatic hydrocarbon (e.g. benzene, toluene or xylene) as the solventand subjecting the by-produced water to azeotropic distillation. Theresulting compound (II) can be isolated and purified by per seconventional means (e.g. extraction, distillation, recrystallization,chromatography, etc.).

The process of Step (B) is carried out by reacting theaminocyclohexenone compound (II) obtained in Step (A) (i) with the aminecompound (V) and formaldehyde (hereinafter this reaction is referred toreaction of Step (B)-(i)), or (ii) with the aminomethanol compound (VI)(hereinafter this reaction is referred to reaction of Step (B)-(ii)).

In the reaction of Step (B)-(i), the amount of the compound (V) orformaldehyde is generally one or more moles per mole of the compound(II), and there is practically no upper limit thereof. However, forpractical purposes, it is desirable to employ about 1 to about 2 molesof the compound (V) or formaldehyde per mole of the compound (II). Theformaldehyde employable in this reaction may be paraformaldehyde.Moreover, while in the reaction the compound (V) is ordinarily employedin a form of hydrochloride, the compound may also be employed in a formof free base with or without hydrochloric acid of a suitableconcentration (e.g. about 20 to about 40% by weight). The reaction ofStep (B)-(i) is preferably conducted in a solvent and at roomtemperature for about 0.5 to about 100 hours. As the solvent, any onemay be employed if it is not detrimental to the reaction, and there maybe exemplified by the same solvents as employed in the reaction of Step(A). The reaction conditions such as temperature and time are notcritical, and the reaction may be, if necessary, conducted at atemperature either higher than or below a room temperature for anextended period of time. Moreover while the reaction of Step (B)-(i) canbe conducted by merely allowing to contact with the compound (II),compound (V) and formaldehyde each other, the reaction may beaccelerated and conducted more smoothly by employing the condensingagents similar to those mentioned for the reaction of Step (A).

In the reaction of Step (B)-(ii), the amount of the compound (VI) isgenerally one or more moles per mole of the compound (II), and there ispractically no upper limit thereof. However, for practical purposes, itis desirable to employ about 1 to about 2 moles of the compound (VI) permole of the compound (II). The reaction of Step (B)-(ii) is preferablyconducted in a solvent and at room temperature for about 0.5 to about 50hours. As the solvent, any one may be employable if it is notdetrimental to the reaction, and there may be exemplified by the samesolvents as employed in the reacton of Step (A). The reaction conditionssuch as temperature and time are not critical, and the reaction may be,if necessary, conducted at a temperature either higher than or below aroom temperature for an extended period of time. On some occasion, thereaction may be accelerated and conducted more smoothly by employing acondensing agent similar to those mentioned for the reaction of Step(A).

The thus produced object compounds (I) can be isolated and purified byper se conventional procedures (e.g. extraction, distillation,recrystallization, chromatography, etc.). When the compounds (II) or theobject compounds (I) are free bases, they may be converted to thecorresponding acid addition salts by per se conventional procedures,which may involve the use of a suitable acid, e.g. an inorganic acid(hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid,carbonic acid, hydrobromic acid, etc.) or an organic acid (acetic acid,oxalic acid, succinic acid, maleic acid, fumaric acid, malic acid,tartaric acid, malonic acid, citric acid, etc.) (for example, bycontacting the base with such an acid in a solvent similar to that usedin the above reactions of Steps (A) and (B)). On the contrary, ifnecessary, the acid addition salts of the compounds (I) may be convertedto the corresponding free bases by per se conventional means such ashydrolyzing the salts with a suitable basic substance (e.g. sodiumhydroxide, sodium carbonate).

The object compounds (I) or their salts which can thus be obtained bythe process of this invention have pharmacological actions such asanalgesic, sedative, tranquillizing, antipyretic, anticonvulsive andantitussive actions in mammals and moreover have an action to depressthe blood sugar levels in mammals, and therefore, are of use as suchdrugs as analgesics, sedatives, tranquillizers, antipyretics,anticonvulsants, antitussives and drugs for the treatment of diabetes.Further, compound of the general formula (II) are not only useful asintermediates for the synthesis of various drugs including compounds(I), but the compounds (II) or salts thereof have pharmacologicalactions such as analgesic and sedative actions as do the compounds (I),and, therefore, are of use as drugs such as analgesics, sedatives andthe like.

When the compounds (I) or the salts thereof are used as drugs of thetype mentioned above, they may be administered per se or in the form ofa pharmaceutically acceptable composition in admixture with a suitableand conventional inert vehicle or adjuvant either orally orparenterally. The pharmaceutical composition may take the form ofpowders, granules, tablets, capsules, solutions, suppositories,injections and so forth.

While the usual daily dosages of the compound (I) or the salt thereofdepends upon such factors as the type of the compound, the kind ofdisease and symptoms, it lies in the range of about 1 to about 1,000 mg.more precisely of about 10 to about 1,000 mg. upon oral administrationand about 1 to about 300 mg. upon parenteral administration per adulthuman.

Conventional methods for obtaining dimedone, a typical compound fallingwithin the scope of the general formula (III), can be applied to theproduction of any compounds (III). Similarly, conventional method forobtaining known compounds falling within the scope of the generalformulas (IV) and (V) can be applied to the production of any compounds(IV) and (V). Moreover, the aminomethanol compounds (VI) may be producedby, for example, the method of E. R. Alexander et al, which is describedin J. Am. Chem. Soc. 71, 4014 (1949).

For a further explanation of the present invention, the followingReference and Examples are given, wherein the word "part(s)" is based onweight unless otherwise noted and the relashionship between "part(s)"and "volume part(s)" corresponds to that between "gram(s)" and"milliliter(s)".

In the following examples, the recrystallization of the compounds (II)and (I) may be carried out by using suitable organic solvents such asketones (e.g. acetone, methyl isopropyl ketone, methyl ethyl ketone),alcohols (e.g. ethanol, methanol, isopropanol, propanol, butanol),ethers (e.g. isopropyl ether, tetrahydrofuran, dioxane, methyl ether,ethyl ether), hydrocarbons (e.g. benzene, xylene, toluene), esters (e.g.ethyl acetate, methyl acetate) or suitable mixtures thereof.

Reaction of Step (A) EXAMPLE 1

a. A mixture of 12.75 parts of 2-chloroaniline and 14 parts of dimedoneis dissolved in 40 volume parts of ethanol under warming, followed bythe addition of 3 drops of glacial acetic acid. The solution is refluxedin a water bath for 2 hours, after which time the ethanol is distilledoff and the resulting residue is allowed to cool, whereupon yellowcrystals separate. These crystals are collected by filtration, washedwith ispropyl ether and recrystallized from acetone. The procedureyields 3-(2-chloroanilino-5,5-dimethyl-2-cyclohexen-1-one as colorlessprisms melting at 150°-152°C. Elementary analysis: C₁₄ H₁₆ NOCL Calcd.C, 67.32; H, 6.45; N, 5.60 Found C, 67.13; H, 6.31; N, 5.82 (b) Amixture of 40 parts of dimedone and 36.4 parts of 2-chloroaniline isheated at 170°-175°C for 45 minutes followed by cooling. The resultingreaction product is recrystallized to obtain yellow cubes. The crystalsare collected by filtration, washed well with isopropyl ether andrecrystallized from acetone. The procedure yields colorless prisms of3-(2-chloroanilino)-5,5-dimethyl-2-cyclohexen-1-one. Melting point:150°-152°C. By procedures similar to those described in Example 1-(a)and (b), the following compounds are produced.

    ______________________________________                                                                       Melting                                        Starting compound                                                                          Product           point                                                                         (°C)                                    ______________________________________                                        Dimedone     3-(3-Chloroanilino)-5,                                                                          147-                                                        5-dimethyl-2-cyclohexen-                                                                         148.5                                         +            1-one                                                            3-Chloroaniline                                                               Dimedone     3-(4-Chloroanilino)-5,5-                                                                        211-                                                        dimethyl-2-cyclohexen-1-                                                                         212                                           +            one                                                              4-Chloroaniline                                                               Dimedone     3-(3-Methoxyanilino)-5,                                                                         118-                                                        5-dimethyl-2-cyclohexen-                                                                         121                                           +            1-one                                                            3-Methoxyaniline                                                              Dimedone     3-(4-Methoxyanilino)-5,5-                                                     dimethyl-2-cyclohexen-1-                                                                        193                                            +            one                                                              4-Methoxyaniline                                                              Dimedone     3-(4-Ethoxyanilino)-5,5-                                                      dimethyl-2-cyclohexen-1-                                                                        165                                            +            one                                                              4-Ethoxyaniline                                                               1,3-Cyclohexanedione                                                                       3-(2-Chloroanilino)-2-                                                                          169-                                                        cyclohexen-1-one   170                                           2-Chloroaniline                                                               1,3-Cyclohexanedione                                                                       3-(3-Chloroanilino)-2-                                                                          158-                                                        cyclohexen-1-one   159                                           +                                                                             3-Chloroaniline                                                               5-Phenylcyclohexane-                                                                       3-Ethylamino-5-phenyl-2-                                                                        174-                                           1,3-dione    cyclohexen-1-one   175                                           +                                                                             Aqueous solution of                                                           ethylamine                                                                    5-Phenylcyclohexane-                                                                       3-Phenethylamino-5-                                              1,3-dione    phenyl-2-cyclohexen-1-                                                                          168                                            +            one                                                              Phenethylamine                                                                5-Phenylcyclohexane-                                                                       3-Cyclohexylamino-5-                                                                            217-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           218                                           +            one                                                              Cyclohexylamine                                                               5-Phenylcyclohexane-                                                                       3-Anilino-5-phenyl-2-                                                                           242-                                           1,3-dione    cyclohexen-1-one   243                                           +                                                                             Aniline                                                                       5-Phenylcyclohexane-                                                                       3-(4-Chloroanilino)-5-                                                                          241-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           242                                           +            one                                                              4-Chloroaniline                                                               5-Phenylcyclohexane-                                                                       3-(2-Chloroanilino)-5-                                                                          174-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           176                                           +            one                                                              2-Chloroaniline                                                               5-Phenylcyclohexane-                                                                       3-(4-Methoxyanilino)-5-                                                                         226-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           228                                           +            one                                                              4-Methoxyaniline                                                              5-Phenylcyclohexane-                                                                       3-(4-Ethoxyanilino)-5-                                                                          203-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           204                                           +            one                                                              4-Ethoxyaniline                                                               5-Phenylcyclohexane-                                                                       3-(2-Ethoxyanilino)-5-                                                                          185-                                           1,3-dione    phenyl-2-cyclohexen-1-                                                                           186                                           +            one                                                              2-Ethoxyaniline                                                               Cyclohexane-1,3-                                                                           3-(4-Chloroanilino)-2-                                           dione        cyclohexen-1-one  192                                            +                                                                             4-Chloroaniline                                                               Cyclohexane-1,3-                                                                           3-(4-Hydroxyanilino)-2-                                                                         230-                                           dione        cyclohexen-1-one   233                                           +                              (decomp.)                                      4-Hydroxyaniline                                                              Cyclohexane-1,3-                                                                           3-(3-Methoxyanilino)-2-                                          dione        cyclohexen-1-one  120                                            +                                                                             3-Methoxyaniline                                                              Cyclohexane-1,3-                                                                           3-(4-Methoxyanilino)-2-                                                                         159-                                           dione        cyclohexen-1-one   160                                           +                                                                             4-Methoxyaniline                                                              Cyclohexane-1,3-                                                                           3-(2-Ethoxyanilino)-2-                                                                          97-98                                          dione        cyclohexen-1-one                                                 +                                                                             2-Ethoxyaniline                                                               Cyclohexane-1,3-                                                                           3-(3-Ethoxyanilino)-2-                                                                          132-                                           dione        cyclohexen-1-one   133                                           +                                                                             3-Ethoxyaniline                                                               Cyclohexane-1,3-                                                                           3-(3-Methylanilino)-2-                                                                          139-                                           dione        cyclohexen-1-one   141                                           +                                                                             3-Methylaniline                                                               Cyclohexane-1,3-                                                                           3-(4-Methylanilino)-2-                                                                          133-                                           dione        cyclohexen-1-one   134                                           +                                                                             4-Methylaniline                                                               5-Methylcyclohexane-                                                                       3-(3-Methoxyanilino)-5-                                                                         149-                                           1,3-dione    methyl-2-cyclohexen-1-                                                                           150                                           +            one                                                              3-Methoxyaniline                                                              5-Methylcyclohexane-                                                                       3-(2-Methylanilino)-5-                                                                          175-                                           1,3-dione    methyl-2-cyclohexen-1-                                                                           176                                           +            one                                                              2-Methylaniline                                                               ______________________________________                                    

Reaction of Step (B) (i) Reaction of Step (B)-(i) EXAMPLE 2

In 10 volume parts of methanol is dissolved 2.15 parts of3-anilino-5,5-dimethyl-2-cyclohexen-1-one under warming and, then, tothe resulting solution 0.9 part of a 37 weight % aqueous solution offormaldehyde, 1.12 part of a 40 weight % aqueous solution ofdimethylamine and 1 drop of glacial acetic acid are added. The wholemixture is allowed to stand at room temperature for 1 hour, after whichtime the methanol is distilled off under reduced pressure. A smallamount of isopropanol is added to the resulting residue and the wholemixture is cooled, whereupon colorless crystals separate. The crystalsare collected by filtration and recrystallized from isopropyl ether toobtain colorless prisms of3-anilino-5,5-dimethyl-2-dimethylaminomethyl-2-cyclohexen-1-one. Meltingpoint: 111°-112°C. Elementary analysis: C₁₇ H₂₄ N₂ O Calcd. C, 74.95; H,8.88; N, 10.28 Found C, 75.28; H, 8.96; N, 10.50.

By procedures similar to those described in Example 2, the followingcompounds are produced.

    ______________________________________                                                                        Melting                                       Starting compound                                                                          Product            point                                                                         (°C)                                   ______________________________________                                        3-Anilino-5,5-                                                                             3-Anilino-5,5-dimethyl-                                                                          110-                                          dimethyl-2-  2-diethylaminomethyl-2-                                                                           111                                          cyclohexen-1-one +                                                                         cyclohexen-1-one                                                 diethylamine +                                                                formaldehyde                                                                  3-Anilino-5,5-                                                                             3-Anilino-5,5-dimethyl-2-                                                                        134-                                          dimethyl-2-  piperidinomethyl-2-                                                                               136                                          cyclohexen-1-one +                                                                         cyclohexen-1-one                                                 piperidine +                                                                  formaldehyde                                                                  3-Anilino-5,5-                                                                             3-Anilino-5,5-dimethyl-                                                                          161-                                          dimethyl-2-  2-morpholinomethyl-2-                                                                             162                                          cyclohexen-1-one +                                                                         cyclohexen-1-one                                                 morpholine +                                                                  formaldehyde                                                                  3-Anilino-5,5-                                                                             3-Anilino-5,5-dimethyl-                                                                          135-                                          dimethyl-2-  2-(4-β-hydroxyethyl-                                                                         136                                          cyclohexen-1-one +                                                                         piperazino)methyl-2-                                             4-β-hydroxyethyl-                                                                     cyclohexen-1-one                                                 piperazine +                                                                  formaldehyde                                                                  ______________________________________                                    

3-(3-Chloroanilino)-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-one.Melting point 123°-124°C

3-(2-Methylanilino)-5-phenyl-2-(3-methylpiperidino)methyl-2-cyclohexen-1-one.Melting point: 125°-128°C

3-(2-Ethoxyanilino)-5-phenyl-2-(N-methyl-N-benzylamino)-methyl-2-cyclohexen-1-one.Melting point: 144°-145°C

3-(2-Ethoxyanilino)-5-phenyl-2-morpholinomethyl-2-cyclohexen-1-one.Melting point: 160°-162°C

3-(2-Methoxyanilino)-5-phenyl-2-piperidinomethyl-2-cyclohexen-1-one.Melting point: 168°-170°C

3-(2-Methoxyanilino)-5-phenyl-2-morpholinomethyl-2-cyclohexen-1-one.Melting point: 200°-203°C

3-(2-Methoxyanilino)-5-phenyl-2-(N-methyl-N-benzylamino)-methyl-2-cyclohexen-1-one.Melting point: 179°-181°C

3-(2-Methoxyanilino)-5-phenyl-2-(4-methylpiperidino)-methyl-2-cyclohexen-1-one.Melting point: 165°-167°C

3-(2-Methoxyanilino)-5-phenyl-2-(3-methylpiperidino)-methyl-2-cyclohexen-1-one.Melting point: 164°-166°C

EXAMPLE 3

2.15 Parts of 3-anilino-5,5-dimethyl-2-cyclohexen-1-one is dissolved in10 volume parts of methanol under warming and, then, to the resultingsolution 0.9 part of a 37 weight % aqueous solution of formaldehyde,0.81 part of dimethylamine hydrochloride and 1 drop of glacial aceticacid are added. The whole mixture is allowed to stand at roomtemperature for 1 hour, and after which time, the methanol is distilledoff under reduced pressure. To the resulting residue is added, a smallamount of isopropyl ether, followed by cooling, whereupon colorlesscrystals separate. The crystals are collected by filtration andrecrystallizd from acetone. The procedure yields colorless needles of3-anilino-5,5-dimethyl-2-dimethylaminomethyl-2-cyclohexen-1-onehydrochloride. Melting point: 169°-170°C Elementary analysis: C₁₇ H₂₅ N₂OC l Calcd. C, 66.10; H, 8.15; N, 9.07 Found C, 66.09; H, 8.21; N, 8.97.

EXAMPLE 4

12.5 Parts of 3-(2-chloroanilino)-5,5-dimethyl-2-cyclohexen-1-one isdissolved in 30 volume parts of methanol under warming and, then, to theresulting solution are added 4.5 parts of a 37 weight % aqueous solutionof formaldehyde, 6.05 parts of piperidine hydrochloride and 2 drops ofglacial acetic acid. The whole mixture is allowed to stand at roomtemperature for 1 hour, whereupon a yellow, clear solution is obtained.The methanol is distilled off under reduced pressure, and a small amountof isopropyl ether is added to the resulting residue, followed bycooling, whereupon colorless crystals separate. The crystals arecollected by filtration and recrystallized from acetone. The procedureyields colorless prisms of3-(2-chloroanilino)-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-onehydrochloride. Melting point: 105°-106°C. Elementary analysis: C₂₀ H₂₈N₂ OCl₂.1/2H₂ O Calcd. C, 61.21; H, 7.45; N, 7.14 Found C, 60.91; H,7.60; N, 7.25.

By procedures similar to those described in Examples 3 and 4, thefollowing compounds are produced.

    ______________________________________                                                                       Melting                                        Starting compound                                                                          Product           point                                                                         (°C)                                    ______________________________________                                        3-(2-Chloroanilino)-                                                                       3-(2-Chloroanilino)-5,5-                                                                        172-                                           5,5-dimethyl-2-                                                                            dimethyl-2-dimethyl-                                                                             173                                           cyclohexen-1-one +                                                                         aminomethyl-2-                                                   dimethylamine                                                                              cyclohexen-1-one                                                 hydrochloride +                                                                            hydrochloride                                                    formaldehyde                                                                  3-(4-Chloroanilino)-                                                                       3-(4-Chloroanilino)-5,5-                                                                        188-                                           5,5-dimethyl-2-                                                                            dimethyl-2-dimethyl-                                                                             205                                           cyclohexen-1-one +                                                                         aminomethyl-2-    (decomp.)                                      dimethylamine                                                                              cyclohexen-1-one                                                 hydrochloride +                                                                            hydrochloride                                                    formaldehyde                                                                  3-(4-Chloroanilino)-                                                                       3-(4-Chloroanilino)-5,5-                                         5,5-dimethyl-2-                                                                            dimethyl-2-piperidino-                                                                          142                                            cyclohexen-1-one +                                                                         methyl-2-cyclohexen-1-                                                                          (decomp.)                                      piperidine   one hydrochloride                                                hydrochloride +                                                               formaldehyde                                                                  3-(3-Methoxyanilino)-                                                                      3-(3-Methoxyanilino)-5,5-                                                                       115-                                           5,5-dimethyl-2-                                                                            dimethyl-2-dimethyl-                                                                             160                                           cyclohexen-1-one +                                                                         aminomethyl-2-cyclohexen-                                                                       (decomp.)                                      dimethylamine                                                                              1-one hydrochloride                                              hydrochloride +                                                               formaldehyde                                                                  3-Methylamino-5,5-                                                                         3-Methylamino-5,5-dimethyl-                                      dimethyl-2-  2-piperidinomethyl-2-                                                                           189                                            cyclohexen-1-one +                                                                         cyclohexen-1-one                                                 piperidine   hydrochloride                                                    hydrochloride +                                                               formaldehyde                                                                  3-(2-Chloroanilino)-                                                                       3-(2-Chloroanilino)-2-                                                                          176-                                           2-cyclohexen-1-one +                                                                       piperidinomethyl-2-                                                                              177.5                                         piperidine   cyclohexen-1-one  (decomp.)                                      hydrochloride +                                                                            hydrochloride                                                    formaldehyde                                                                  3-(4-Methoxyanilino)-                                                                      3-(4-Methoxyanilino)-5,5-                                                                       160-                                           5,5-dimethyl-2-                                                                            dimethyl-2-dimethyl-                                                                             165                                           cyclohexen-1-one +                                                                         aminomethyl-2-                                                   dimethylamine                                                                              cyclohexen-1-one                                                 hydrochloride +                                                                            hydrochloride                                                    formaldehyde                                                                  ______________________________________                                    

EXAMPLE 5

2.15 Parts of 3-anilino-5,5-dimethyl-2-cyclohexen-1-one is dissolved in10 volume parts of methanol under heating and, then, to the resultingsolution are added 0.9 part of a 37 weight % aqueous solution offormaldehyde, 0.87 part of morpholine and 1.6 part of 20 weight %hydrochloric acid. The mixture is allowed to stand at room temperaturefor 1 hour, after which time the methanol is distilled off under reducedpressure, whereupon yellow crystals separate. The crystals are collectedby filtration, washed with isopropyl ether and recrystallized fromacetone. The procedure yields colorless scales of3-anilino-5,5-dimethyl-2-morpholinomethyl-2-cyclohexen-1-onehydrochloride. Melting point: 172°-173°C Elementary analysis: C₁₉ H₂₇ N₂O₂ Cl.H₂ O Calcd. C, 61.85; H, 7.92; N, 7.59 Found C, 61.88; H, 7.87; N,7.67.

EXAMPLE 6

2.15 Parts of 3-anilino-5,5-dimethyl-2-cyclohexen-1-one is dissolved in10 volume parts of methanol under warming and, then, to the resultingsolution are added 0.9 part of a 37 weight % aqueous solution offormaldehyde, 1.3 parts of N-(β-hydroxyethyl) piperazine and 1.6 partsof 20 weight % hydrochloric acid. The whole mixture is allowed to standat room temperature for 1 hour. After which time, the methanol isdistilled off under reduced pressure, and isopropyl ether is added tothe resulting residue, followed by cooling, whereupon pale yellowcrystals separate. The crystals are collected by filtration andrecrystallized from acetone. The procedure yields colorless powderycrystals of3-anilino-5,5-dimethyl-2-(4-B-hydroxyethyl-piperazino)methyl-2-cyclohexen-1-onehydrochloride. Melting point: 172°-173°C. Elementary analysis: C₂₁ H₃₂N₃ O₂ Cl Calcd. C, 64.02; H, 8.18; N, 10.66 Found C, 64.18; H, 8.28; N,10.95.

(ii) Reaction of Step (B)-(ii) EXAMPLE 7

In 20 volume parts of methanol is dissolved 4.3 parts of3-anilino-5,5-dimethyl-2-cyclohexen-1-one, followed by the addition of2.3 parts of dimethylaminomethanol. The resulting mixture is allowed tostand at room temperature for 1 hour, after which time the methanol isdistilled off under reduced pressure. The resulting residue is caused tocrystallize by the addition of isopropyl ether. The isopropylether-soluble fraction is separated from the insolubles, and the solublefraction is concentrated to recover a crude product of3-anilino-5,5-dimethyl-2-dimethylaminomethyl-2-cyclohexan-1-one. Theresulting crude product is recrystallized from isopropyl ether to yieldcolorless prisms melting at 118°-119°C. Elementary analysis: C₁₇ H₂₄ N₂O Calcd. C, 74.95; H, 8.88; N, 10.28 Found C, 75.12; H, 8.98; N, 10.16.By procedures similar to those described in Example 7, the followingcompounds are produced from the corresponding aminocyclohexenonecompounds (II) and aminomethanol compounds (VI).

3-Anilino-5,5-dimethyl-2-diethylaminomethyl-2-cyclohexen-1-one. Meltingpoint: 110°-111°C

3-Anilino-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-one. Meltingpoint: 134°-136°C

3-Anilino-5,5-dimethyl-2-morpholinomethyl-2-cyclohexen-1-one. Meltingpoint: 161°-162°C

3-Anilino-5,5-dimethyl-2-(4β-hydroxyethylpiperazino)-methyl-2-cyclohexen-1-one. Melting point:135°-136°C

3-(3-Chloroanilino)-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-one.Melting point: 123°-124°C

3-(2-Methylanilino)-5-phenyl-2-(3-methylpiperidino)-methyl-2-cyclohexen-1-one.Melting point: 125°-128°C

3-(2-Ethoxyanilino)-5-phenyl-2-(N-methyl-N-benzylamino)-methyl-2-cyclohexen-1-one.Melting point: 144°-145°C

3-(2-Ethoxyanilino)-5-phenyl-2-morpholinomethyl-2-cyclohexen-1-one.Melting point: 160°-162°C

3-(2-Methoxyanilino)-5-phenyl-2-piperidinomethyl-2-cyclohexen-1-one.Melting point: 168°-170°C

3-(2-Methoxyanilino)-5-phenyl-2-morpholinomethyl-2-cyclohexen-1-one.Melting point: 200°-203°C

3-(2-Methoxyanilino)-5-phenyl-2-(N-methyl-N-benzylamino)-methyl-2-cyclohexen-1-one.Melting point: 179°-181°C

3-(2-Methoxyanilino)-5-phenyl-2-(4-methylpiperidino)-methyl-2-cyclohexen-1-one.Melting point: 165°-167°C

3-(2-Methoxyanilino)-5-phenyl-2-(3-methylpiperidino)-methyl-2-cyclohexen-1-one.Melting point: 164°-166°C

EXAMPLE 8

In 20 volume parts of methanol is dissolved 4.6 parts of3-(4-ethoxyanilino)-2-cyclohexen-1-one, followed by the addition of 3.2parts of diethylaminomethanol. The resulting mixture is allowed to standat room temperature for 2 hours, after which time the methanol isdistilled off. To the residue is added isopropyl ether and the resultingresinous precipitate is filtered off. The filtrate is concentrated, andto the resultant 6.6 volume parts of 10 % ethanolic hydrochloric acid isadded, followed by further concentration. Ethyl acetate is added to theresulting concentrate and the separated crystals are collected byfiltration. Recrystallization from a mixture of ethyl acetate andmethanol yields colorless prisms of3-(4-ethoxyanilino)-2-diethylaminomethyl-2-cyclohexen-1-onehydrochloride melting at 127°-130°C (decomp.). Elementary analysis: C₁₉H₂₈ N₂ O₂.HCl Calcd. C, 64.67; H, 8.28; N, 7.94 Found C, 64.69; H, 8.50;N, 8.11.

By procedures similar to those described in Examples 3 to 6 (i.e. by thereaction of Step (B)-(i)) or in the Examples 7 to 8 (i.e. by thereaction of Step (B)-(ii), the following compounds are produced from thecorresponding aminocyclohexenone compounds (II), the amine compounds (V)and formaldehyde, or from the corresponding aminocyclohexenone compounds(II) and aminomethanol compound (VI).

    ______________________________________                                                                 Reaction(s) by                                                                which the                                            Compound                 compound is                                                                   produced                                             ______________________________________                                        3-Anilino-5,5-dimethyl-2-dimethyl-                                                                     Reaction of                                          aminomethyl-2-cyclohexen-1-one                                                                         Step(B)-(ii)                                         hydrochloride. Melting point:                                                 169-170°C                                                              3-Anilino-5,5-dimethyl-2-                                                                              Reaction of                                          morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(ii)                                         one hydrochloride.                                                            Melting point: 172-173°C(decomp.)                                      3-Anilino-5,5-dimethyl-2-(4-β-                                                                    Reaction of                                          hydroxyethylpiperazino)methyl-2-                                                                       Step(B)-(ii)                                         cyclohexen-1-one hydrochloride.                                               Melting point: 172-173°C                                               3-(2-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(ii)                                         1-one hydrochloride.                                                          Melting point: 172-173°C                                               3-(2-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(ii)                                         one hydrochloride.                                                            Melting point: 105-106°C                                               3-(2-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 189°C(decomp.)                                          3-(2-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         (4-β-hydroxyethylpiperazino)-                                                                     Step(B)-(i)                                          methyl-2-cyclohexen-1-one                                                                              and (ii)                                             hydrochloride 1/2 hydrate.                                                    Melting point: 131°C                                                   3-(3-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         dimethylaminomethyl-2-cyclohexen-                                                                      Step (B)-(i)                                         1-one hydrochloride.     and (ii)                                             Melting point: 176°C                                                   3-(3-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         diethylaminomethyl-2-cyclohexen-                                                                       Step (B)-(i)                                         1-one hydrochloride.     and (ii)                                             Melting point: 140°C                                                   3-(3-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step (B)-(i)                                         one hydrochloride.       and (ii)                                             Melting point: 182-183.5°C(decomp.)                                    3-(4-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(ii)                                         1-one hydrochloride.                                                          Melting point: 188-205°C(decomp.)                                      3-(4-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         diethylaminomethyl-2-cyclohexen-                                                                       Step(B)-(i)                                          1-one hydrochloride 1/2 hydrate.                                                                       and (ii)                                             Melting point: 141°C(decomp.)                                          3-(4-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(ii)                                         one hydrochloride.                                                            Melting point: 142°C(decomp.)                                          3-(4-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 141°C(decomp.)                                          3-(4-Chloroanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         (N-methyl-N-benzylamino)methyl-2-                                                                      Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 186°C(decomp.)                                          3-(2-Hydroxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 177-178°C(decomp.)                                      3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reaction of                                          dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(ii)                                         one hydrochloride.                                                            Melting point: 160-165°C(decomp.)                                      3-(2-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 162-164°C(decomp.)                                      3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         diethylaminomethyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 129-132°C(decomp.)                                      3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 107-109°C                                               3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 134-137°C                                               3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         (N-methyl-N-benzylamino)methyl-2-                                                                      Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 160-161°C(decomp.)                                      3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         (N-methyl-N-phenethylamino)methyl-                                                                     Step(B)-  (i)                                        2-cyclohexen-1-one hydrochloride.                                                                      and (ii)                                             Melting point: 112-118°C(decomp.)                                      3-(4-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reaction of                                          dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(ii)                                         1-one hydrochloride.                                                          Melting point: 160-165°C                                               3-(4-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 110-117°C                                               3-(4-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 134-137°C                                               3-(2-Ethoxyanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 147-149°C(decomp.)                                      3-(4-Ethoxyanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 179-180°C                                               3-(4-Ethoxyanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 185°C                                                   3-(4-Ethoxyanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         (N-methyl-N-benzylamino)methyl-2-                                                                      Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 152-157°C(decomp.)                                      3-(4-Ethoxyanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         (N-methyl-N-phenethylamino)methyl-                                                                     Step(B)-(i)                                          2-cyclohexen-1-one hydrochloride                                                                       and (ii)                                             hydrate. Melting point: 160-165°C                                      3-(2-Methylanilino)-5,5-dimethyl-2-                                                                    Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/4 hydrate.                                                                         and (ii)                                             Melting point: 167-168°C(decomp.)                                      3-Methylamino-5,5-dimethyl-2-dimethyl-                                                                 Reactions of                                         aminomethyl-2-cyclohexen-1-one                                                                         Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 186°C                                                   3-Methylamino-5,5-dimethyl-2-diethyl-                                                                  Reactions of                                         aminomethyl-2-cyclohexen-1-one                                                                         Step(B)-(i)                                          hydrochloride. Melting point: 191°C                                                             and (ii)                                             3-Methylamino-5,5-dimethyl-2-                                                                          Reaction of                                          piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(ii)                                         one hydrochloride.                                                            Melting point: 189°C                                                   3-Methylamino-5,5-dimethyl-2-                                                                          Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 178°C                                                   3-Anilino-2-dimethylaminomethyl-2-                                                                     Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 140-143°C(decomp.)                                                               and (ii)                                             3-Anilino-2-diethylaminomethyl-2-                                                                      Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 128-131°C(decomp.)                                                               and (ii)                                             3-Anilino-2-piperidinomethyl-2-                                                                        Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 163-166°C(decomp.)                                                               and (ii)                                             3-Anilino-2-morpholinomethyl-2-                                                                        Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 141-143°C(decomp.)                                                               and (ii)                                             3-(2-Chloroanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 142-144°C(decomp.)                                      3-(2-Chloroanilino)-2-piperidinomethyl-                                                                Reaction of                                          2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(ii)                                         Melting point: 176-177.5°C                                             3-(2-Chloroanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 164-165°C(decomp.)                                                               and (ii)                                             3-(2-Chloroanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 165-167°C(decomp.)                                      3-(2-Chloroanilino)-2-(N-methyl-N-                                                                     Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 152-153°C(decomp.)                                      3-(2-Chloroanilino)-2-(4-methyl-                                                                       Reactions of                                         piperazino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 173-175°C(decomp.)                                      3-(2-Chloroanilino)-2-(4-methyl-                                                                       Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 163-165°C                                               3-(3-Chloroanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 162°C(decomp.)                                          3-(3-Chloroanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 184°C(decomp.)                                                                   and (ii)                                             3-(3-Chloroanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 172°C(decomp.)                                                                   and (ii)                                             3-(3-Chloroanilino)-2-(4-β-hydroxyethyl-                                                          Reactions of                                         piperazino)methyl-2-cyclohexen-1-one                                                                   Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 173°C(decomp.)                                          3-(4-Chloroanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 167°C(decomp.)                                          3-(4-Chloroanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride 1/2                                                                   Step(B)-(i)                                          hydrate.                 and (ii)                                             Melting point: 135-136°C(decomp.)                                      3-(4-Chloroanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 170-172°C(decomp.)                                                               and (ii)                                             3-(4-Chloroanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 184-185°C(decomp.)                                      3-(4-Chloroanilino)-2-(N-methyl-N-                                                                     Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 149-150°C(decomp.)                                      3-(4-Hydroxyanilino)-2-dimethylamino-                                                                  Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 170-173°C(decomp.)                                      3-(4-Hydroxyanilino)-2-diethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 166-169°C(decomp.)                                      3-(4-Hydroxyanilino)-2-piperidinomethyl-                                                               Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 177-180°C(decomp.)                                                               and (ii)                                             3-(4-Hydroxyanilino)-2-(N-methyl-N-                                                                    Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 154-156°C(decomp.)                                      3-(2-Methoxyanilino)-2-dimethylamino-                                                                  Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 166°C(decomp.)                                          3-(2-Methoxyanilino)-2-piperidinomethyl-                                                               Reactions of                                         2-cyclohexen-1-one hydrochloride 1/4                                                                   Step(B)-(i)                                          hydrate.                 and (ii)                                             Melting point: 187-188°C(decomp.)                                      3-(2-Methoxyanilino)-2-morpholinomethyl-                                                               Reactions of                                         2-cyclohexen-1-one hydrochloride 1/2                                                                   Step(B)-(i)                                          hydrate.                 and (ii)                                             Melting point: 176°C(decomp.)                                          3-(2-Methoxyanilino)-2-(4-β-hydroxy-                                                              Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 169-170°C(decomp.)                                      3-(2-Methoxyanilino)-2-(N-methyl-N-                                                                    Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride 1/4 hydrate.                                                                         and (ii)                                             Melting point: 160-161°C(decomp.)                                      3-(3-Methoxyanilino)-2-dimethylamino-                                                                  Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 120-121°C(decomp.)                                      3-(3-Methoxyanilino)-2-piperidinomethyl-                                                               Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 148-151°C(decomp.)                                                               and (ii)                                             3-(3-Methoxyanilino)-2-morpholinomethyl-                                                               Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 147°C(decomp.)                                                                   and (ii)                                             3-(3-Methoxyanilino)-2-(4-β-hydroxy-                                                              Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 141-143°C(decomp.)                                      3-(3-Methoxyanilino)-2-(4-methyl-                                                                      Reactions of                                         piperazino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 152-153°C(decomp.)                                      3-(3-Methoxyanilino)-2-(4-methyl-                                                                      Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 150-151°C(decomp.)                                      3-(4-Methoxyanilino)-2-dimethylamino-                                                                  Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 166-167°C(decomp.)                                      3-(4-Methoxyanilino)-2-diethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 95-96°C(decomp.)                                        3-(4-Methoxyanilino)-2-piperidino-                                                                     Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 170-171°C(decomp.)                                      3-(4-Methoxyanilino)-2-morpholino-                                                                     Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 168-169°C(decomp.)                                      3-(4-Methoxyanilino)-2-(4-β-hydroxy-                                                              Reactions of                                         ethylpiperazino)methyl-2-                                                                              Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 175-176°C(decomp.)                                      3-(4-Methoxyanilino)-2-(N-methyl-N-                                                                    Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 78-81°C(decomp.)                                        3-(4-Methoxyanilino)-2-(4-methyl-                                                                      Reactions of                                         piperazino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 156-157°C(decomp.)                                      3-(4-Methoxyanilino)-2-(2-methyl-                                                                      Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 120-121°C(decomp.)                                      3-(4-Methoxyanilino)-2-(4-methyl-                                                                      Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride 1/3 hydrate.                                                                         and (ii)                                             Melting point: 105-106°C(decomp.)                                      3-(4-Methoxyanilino)-2-(3-methyl-                                                                      Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 131-132°C(decomp.)                                      3-(2-Ethoxyanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 149-151°C(decomp.)                                      3-(2-Ethoxyanilino)-2-piperidino-                                                                      Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride hydrate.   and (ii)                                             Melting point: 110-112°C(decomp.)                                      3-(2-Ethoxyanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 143-145°C(decomp.)                                                               and (ii)                                             3-(2-Ethoxyanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-                                                                              Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 168-169°C(decomp.)                                      3-(3-Ethoxyanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride hydrate.   and (ii)                                             Melting point: 108-110°C(decomp.)                                      3-(3-Ethoxyanilino)-2-diethylamino-                                                                    Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 140-142°C(decomp.)                                      3-(3-Ethoxyanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 134-136°C(decomp.)                                                               and (ii)                                             3-(3-Ethoxyanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 145-148°C(decomp.)                                                               and (ii)                                             3-(3-Ethoxyanilino)-2-(N-methyl-N-                                                                     Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 144-146°C(decomp.)                                      3-(3-Ethoxyanilino)-2-(4-methyl-                                                                       Reactions of                                         piperazino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 153-155°C(decomp.)                                      3-(3-Ethoxyanilino)-2-(4-methyl-                                                                       Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 154-155°C(decomp.)                                      3-(4-Ethoxyanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 109-111°C(decomp.)                                      3-(4-Ethoxyanilino)-2-diethylamino-                                                                    Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 127-130°C(decomp.)                                      3-(4-Ethoxyanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 145-147°C(decomp.)                                                               and (ii)                                             3-(4-Ethoxyanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 130-132°C(decomp.)                                                               and (ii)                                             3-(4-Ethoxyanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 160-161°C(decomp.)                                      3-(4-Ethoxyanilino)-2-(N-methyl-N-                                                                     Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 134-135°C(decomp.)                                      3-(4-Ethoxyanilino)-2-(2-methyl-                                                                       Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 130-133°C(decomp.)                                      3-(2-Methylanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 157-158°C(decomp.)                                      3-(2-Methylanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 164-165°C(decomp.)                                                               and (ii)                                             3-(2-Methylanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 154-155°C(decomp.)                                                               and (ii)                                             3-(2-Methylanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 170-171°C(decomp.)                                      3-(2-Methylanilino)-2-(4-methyl-                                                                       Reactions of                                         piperidino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 160-161.5°C(decomp.)                                    3-(3-Methylanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 133-135°C(decomp.)                                      3-(3-Methylanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 142-144°C(decomp.)                                                               and (ii)                                             3-(3-Methylanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 164-165°C(decomp.)                                                               and (ii)                                             3-(3-Methylanilino)-2-(4-β-hydroxy-                                                               Reactions of                                         ethylpiperazino)methyl-2-cyclohexen-                                                                   Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 162-163°C(decomp.)                                      3-(3-Methylanilino)-2-(N-methyl-N-                                                                     Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 132-133°C(decomp.)                                      3-(4-Methylanilino)-2-dimethylamino-                                                                   Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 190-192°C(decomp.)                                      3-(4-Methylanilino)-2-piperidinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 140-141°C(decomp.)                                                               and (ii)                                             3-(4-Methylanilino)-2-morpholinomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 162-164°C(decomp.)                                                               and (ii)                                             3-(4-Methylanilino)-2-(4-methyl-                                                                       Reactions of                                         piperazino)methyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 182-185°C(decomp.)                                      3-Benzylamino-2-dimethylaminomethyl-                                                                   Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 169-170°C(decomp.)                                                               and (ii)                                             3-Benzylamino-2-piperidinomethyl-2-                                                                    Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 174°C(decomp.)                                                                   and (ii)                                             3-Benzylamino-2-morpholinomethyl-2-                                                                    Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 167°C(decomp.)                                                                   and (ii)                                             3-Benzylamino-2-(N-methyl-N-benzyl-                                                                    Reactions of                                         amino)methyl-2-cyclohexen-1-one                                                                        Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 164-165°C(decomp.)                                      3-Isopropylamino-2-piperidinomethyl-2-                                                                 Reactions of                                         cyclohexen-1-one hydrochloride 1/3                                                                     Step(B)-(i)                                          hydrate.                 and (ii)                                             Melting point: 152-154°C(decomp.)                                      3-Phenethylamino-2-dimethylaminomethyl-                                                                Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 134-137°C(decomp.)                                                               and (ii)                                             3-Phenethylamino-2-piperidinomethyl-2-                                                                 Reactions of                                         cyclohexen-1-one dihydrochloride.                                                                      Step(B)-(i)                                          Melting point: 122-124°C(decomp.)                                                               and (ii)                                             3-Phenethylamino-2-morpholinomethyl-2-                                                                 Reactions of                                         cyclohexen-1-one hydrochloride.                                                                        Step(B)-(i)                                          Melting point: 112-115°C(decomp.)                                                               and (ii)                                             3-Cyclohexylamino-2-dimethylamino-                                                                     Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 169-171°C(decomp.)                                      3-Cyclohexylamino-2-piperidinomethyl-                                                                  Reactions of                                         2-cyclohexen-1-one hydrochloride.                                                                      Step(B)-(i)                                          Melting point: 150-152°C(decomp.)                                                               and (ii)                                             3-(3-Dimethylaminopropylamino)-2-                                                                      Reactions of                                         dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one dihydrochloride.     and (ii)                                             Melting point: 155-158°C(decomp.)                                      3-(3-Dimethylaminopropylamino)-2-                                                                      Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one dihydrochloride.     and (ii)                                             Melting point: 163-165°C(decomp.)                                      3-(3-Dimethylaminopropylamino)-2-                                                                      Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one dihydrochloride.     and (ii)                                             Melting point: 160-162°C(decomp.)                                      3-(2-Chloroanilino)-5-methyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 167-168°C(decomp.)                                      3-(2-Chloroanilino)-5-methyl-2-(4-                                                                     Reactions of                                         methylpiperazino)methyl-2-cyclohexen-                                                                  Step(B)-(i)                                          1-one hydrochloride hydrate.                                                                           and (ii)                                             Melting point: 175-177°C(decomp.)                                      3-(2-Chloroanilino)-5-methyl-2-(4-                                                                     Reactions of                                         methylpiperidino)methyl-2-cyclohexen-                                                                  Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 135-136°C                                               3-(2-Methoxyanilino)-5-methyl-2-                                                                       Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 142-143°C(decomp.)                                      3-(3-Methoxyanilino)-5-methyl-2-                                                                       Reactions of                                         dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 167-169°C(decomp.)                                      3-(3-Methoxyanilino)-5-methyl-2-                                                                       Reactions of                                         diethylaminomethyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 145-147°C(decomp.)                                      3-(3-Methoxyanilino)-5-methyl-2-                                                                       Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 160-163°C(decomp.)                                      3-(3-Methoxyanilino)-5-methyl-2-                                                                       Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 124-125°C(decomp.)                                      3-(3-Methoxyanilino)-5-methyl-2-(N-                                                                    Reactions of                                         methyl-N-benzylamino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 153-154°C(decomp.)                                      3-(2-Ethoxyanilino)-5-methyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 164-166°C(decomp.)                                      3-(2-Methylanilino)-5-methyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 162-164°C(decomp.)                                      3-Anilino-5-phenyl-2-dimethylamino-                                                                    Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 144-145°C                                               3-Anilino-5-phenyl-2-diethylamino-                                                                     Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride hydrate.   and (ii)                                             Melting point: 113-114°C                                               3-Anilino-5-phenyl-2-piperidino-                                                                       Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 139-140°C                                               3-Anilino-5-phenyl-2-morpholinomethyl-                                                                 Reactions of                                         2-cyclohexen-1-one hydrochloride                                                                       Step(B)-(i)                                          hydrate.                 and (ii)                                             Melting point: 147-  149°C                                             3-Anilino-5-phenyl-2-(4-β-hydroxy-                                                                Reactions of                                         ethylpiperazino)methyl-2-                                                                              Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             ethanol adduct.                                                               Melting point: 110-112°C                                               3-Anilino-5-phenyl-2-(N-methyl-N-                                                                      Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 79-80°C                                                 3-(2-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 158-160°C                                               3-(2-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 153-154°C                                               3-(2-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 178-179°C(decomp.)                                      3-(2-Chloroanilino)-5-phenyl-2-(4-                                                                     Reactions of                                         methylpiperazino)methyl-2-cyclo-                                                                       Step(B)-(i)                                          hexen-1-one hydrochloride.                                                                             and (ii)                                             Melting point: 187-189°C                                               3-(2-Chloroanilino)-5-phenyl-2-(4-                                                                     Reactions of                                         methylpiperidino)methyl-2-cyclo-                                                                       Step(B)-(i)                                          hexen-1-one hydrochloride.                                                                             and (ii)                                             Melting point: 165-167°C                                               3-(2-Chloroanilino)-5-phenyl-2-(3-                                                                     Reactions of                                         methylpiperidino)methyl-2-cyclo-                                                                       Step(B)-(i)                                          hexen-1-one hydrochloride hydrate.                                                                     and (ii)                                             Melting point: 141-143°C                                               3-(4-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 183-184°C                                               3-(4-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         diethylaminomethyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 73-74°C                                                 3-(4-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 135-137°C                                               3-(4-Chloroanilino)-5-phenyl-2-                                                                        Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 159-161°C                                               3-(4-Chloroanilino)-5-phenyl-2-(4-β-                                                              Reactions of                                         hydroxyethylpiperazino)methyl-2-                                                                       Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             1/2 hydrate.                                                                  Melting point: 133-134°C                                               3-(4-Chloroanilino)-5-phenyl-2-(N-                                                                     Reactions of                                         methyl-N-benzylamino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             hydrate.                                                                      Melting point: 136-137°C                                               3-(4-Methoxyanilino)-5-phenyl-2-                                                                       Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 140-141°C                                               3-(4-Methoxyanilino)-5-phenyl-2-                                                                       Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 146-148°C                                               3-(4-Methoxyanilino)-5-phenyl-2-                                                                       Reactions of                                         dimethylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 170-171°C                                               3-(4-Methoxyanilino)-5-phenyl-2-                                                                       Reactions of                                         diethylaminomethyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 141-142°C                                               3-(4-Methoxyanilino)-5-phenyl-2-(4-β-                                                             Reactions of                                         hydroxyethylpiperazino)methyl-2-                                                                       Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             1/2 hydrate.                                                                  Melting point: 118-120°C                                               3-(4-Methoxyanilino)-5-phenyl-2-(N-                                                                    Reactions of                                         methyl-N-benzylamino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             methanol adduct.                                                              Melting point: 115-120°C                                               3-(2-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 170-171°C                                               3-(4-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         dimethylaminomethyl-2-cyclohexen-                                                                      Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 161-162°C                                               3-(4-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         diethylaminomethyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 131-133°C                                               3-(4-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride.       and (ii)                                             Melting point: 175-176°C(decomp.)                                      3-(4-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 160.5-162°C(decomp.)                                    3-(4-Ethoxyanilino)-5-phenyl-2-                                                                        Reactions of                                         (4-β-hydroxyethylpiperazino)methyl-                                                               Step(B)-(i)                                          2-cyclohexen-1-one dihydrochloride                                                                     and (ii)                                             hydrate.                                                                      Melting point: 170-172°C(decomp.)                                      3-(4-Ethoxyanilino)-5-phenyl-2-(N-                                                                     Reactions of                                         methyl-N-benzylamino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             1/2 hydrate.                                                                  Melting point: 110-111°C(decomp.)                                      3-(2-Methylanilino)-5-phenyl-2-                                                                        Reactions of                                         piperidinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride 1/2 ethanol                                                                          and (ii)                                             adduct.                                                                       Melting point: 136-138°C                                               3-(2-Methylanilino)-5-phenyl-2-(4-                                                                     Reactions of                                         methylpiperazino)methyl-2-                                                                             Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 195-198°C(decomp.)                                      3-(2-Methylanilino)-5-phenyl-2-(2-                                                                     Reactions of                                         methylpiperidino)methyl-2-                                                                             Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             acetone adduct.                                                               Melting point: 115-118°C                                               3-(2-Methylanilino)-5-phenyl-2-(4-                                                                     Reactions of                                         methylpiperidino)methyl-2-cyclo-                                                                       Step(B)-(i)                                          hexen-1-one hydrochloride.                                                                             and (ii)                                             Melting point: 171-173°C(decomp.)                                      3-Ethylamino-5-phenyl-2-dimethylamino-                                                                 Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 149-150°C                                               3-Ethylamino-5-phenyl-2-morpholino-                                                                    Reactions of                                         methyl-2-cyclohexen-1-one                                                                              Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 113°C                                                   3-Ethylamino-5-phenyl-2-(N-methyl-N-                                                                   Reactions of                                         benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride 1/2 hydrate.                                                                         and (ii)                                             Melting point: 140-142°C                                               3-Phenethylamino-5-phenyl-2-dimethyl-                                                                  Reactions of                                         aminomethyl-2-cyclohexen-1-one                                                                         Step(B)-(i)                                          hydrochloride 1/2 hydrate.                                                                             and (ii)                                             Melting point: 132°C                                                   3-Phenethylamino-5-phenyl-2-diethyl-                                                                   Reactions of                                         aminomethyl-2-cyclohexen-1-one                                                                         Step(B)-(i)                                          hydrochloride.           and (ii)                                             Melting point: 124-125°C                                               3-Phenethylamino-5-phenyl-2-                                                                           Reactions of                                         piperidinomethyl-2-cyclohexen-                                                                         Step(B)-(i)                                          1-one hydrochloride.     and (ii)                                             Melting point: 113-114°C                                               3-Phenethylamino-5-phenyl-2-                                                                           Reactions of                                         morpholinomethyl-2-cyclohexen-1-                                                                       Step(B)-(i)                                          one hydrochloride hydrate.                                                                             and (ii)                                             Melting point: 120°C                                                   3-Phenethylamino-5-phenyl-2-(4-β-                                                                 Reactions of                                         hydroxyethylpiperazino)methyl-2-                                                                       Step(B)-(i)                                          cyclohexen-1-one hydrochloride                                                                         and (ii)                                             1/2 hydrate.                                                                  Melting point: 132-135°C                                               3-Phenethylamino-5-phenyl-2-(N-                                                                        Reactions of                                         methyl-N-benzylamino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                                                        and (ii)                                             Melting point: 142°C                                                   3-(3-Methoxyanilino)-2-(N-methyl-N-                                                                    Reaction of                                          benzylamino)methyl-2-cyclohexen-                                                                       Step(B)-(i)                                          1-one hydrochloride.                                                          Melting point: 136-138°C(decomp.)                                      3-(2-Methylamino)-2-(N-methyl-N-                                                                       Reaction of                                          benzylamino)methyl-2-cyclohexen-1-                                                                     Step(B)-(i)                                          one hydrochloride.                                                            Melting point: 166-167°C(decomp.)                                      3-(2-Methoxyanilino)-2-pyrrolidino-                                                                    Reaction of                                          methyl-5-phenyl-2-cyclohexen-1-                                                                        Step(B)-(i)                                          one.                                                                          Melting point: 150-151°C                                               3-(2-Chloroanilino)-2-pyrrolidino-                                                                     Reaction of                                          methyl-5-phenyl-2-cyclohexen-1-                                                                        Step(B)-(i)                                          one hydrochloride hydrate.                                                    Melting point: 165-166°C                                               3-(2-Methylanilino)-2-pyrrolidino-                                                                     Reaction of                                          methyl-5-phenyl-2-cyclohexen-1-one.                                                                    Step(B)-(i)                                          Melting point: 140-141°C                                               3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reaction of                                          (N-methyl-N-allylamino)methyl-2-                                                                       Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                               Melting point: 88-91°C                                                 3-(3-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          (N-methyl-N-allylamino)methyl-2-                                                                       Step(B)-(i)                                          cyclohexen-1-one hydrochloride.                                               Melting point: 106-109°C                                               3-(2-Methylanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          benzylaminomethyl-2-cyclohexen-1-                                                                      Step(B)-(i)                                          one hydrochloride.                                                            Melting point: 195-197°C(decomp.)                                      3-Piperidino-5,5-dimethyl-2-                                                                           Reaction of                                          morpholinomethyl-2-cyclohexen-1-one.                                                                   Step(B)-(i)                                          Melting point: 99-101°C                                                3-(3-Chloroanilino)-5,5-dimethyl-2-                                                                    Reaction of                                          (N-methyl-N-phenethylamino)methyl-                                                                     Step(B)-(i)                                          2-cyclohexen-1-one.                                                           Melting point: 105-165°C(decomp.)                                      3-(N-dimethylamino)-5,5-dimethyl-2-                                                                    Reaction of                                          butylaminomethyl-2-cyclohexen-1-one.                                                                   Step(B)-(i)                                          3-(N-methyl-N-benzylamino)-5,5-dimethyl-                                                               Reaction of                                          2-propylaminomethyl-2-cyclohexen-1-                                                                    Step(B)-(i)                                          one                                                                           3-(3-Nitroanilino)-5,5-dimethyl-2-                                                                     Reaction of                                          piperidinomethyl-2-cyclohexen-1-one                                                                    Step(B)-(i)                                          3-(3-Acetylaminoanilino)-5,5-dimethyl-                                                                 Reaction of                                          2-dimethylaminomethyl-2-cyclohexen-                                                                    Step(B)-(i)                                          1-one                                                                         3-(3-Methylaminoanilino)-5,5-dimethyl-                                                                 Reaction of                                          2-dimethylaminomethyl-2-cyclohexen-                                                                    Step(B)-(i)                                          1-one                                                                         3-(3-Dimethylaminoanilino)-5,5-                                                                        Reaction of                                          dimethyl-2-dimethylaminomethyl-2-                                                                      Step(B)-(i)                                          cyclohexen-1-one                                                              3-(2-Chloroanilino)-5,5-dimethyl-2-(4-                                                                 Reaction of                                          hydroxypiperidino)methyl-2-                                                                            Step(B)-(i)                                          cyclohexen-1-one                                                              3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reaction of                                          (4-chloropiperidino)methyl-2-                                                                          Step(B)-(i)                                          cyclohexen-1-one                                                              3-(3-Methoxyanilino)-5,5-dimethyl-2-                                                                   Reaction of                                          (4-methoxypiperidino)methyl-2-                                                                         Step(B)-(i)                                          cyclohexen-1-one                                                              ______________________________________                                    

EXAMPLE 9

Some examples of practical recipes in which the compound of the presentinvention are utilized as analgesics are as follows:

    A.(Tablet)                                                                    (1)       3-(3-methoxyanilino)-5,5-                                                                         10 mg.                                                    dimethyl-2-(N-methyl-N-                                                       phenethylamino)methyl-2-                                                      cyclohexen-1-one hydrochloride                                      (2)       lactose             35 mg.                                          (3)       corn starch         150 mg.                                         (4)       microcrystalline cellulose                                                                        30 mg.                                          (5)       magnesium stearate  5 mg.                                                                         230 mg.                                                                       per tablet                                  

(1), (2), (3), 2/3 quantity of (4) and half quantity of (5) arethroughly mixed, and then the mixture is granulated. Remaining 1/3quantity of (4) and half of (5) are added to the granules and compressedinto tablets. Thus prepared tablets can further be coated with asuitable coating agent, e.g. sugar.

    ______________________________________                                        B.(Capsule)                                                                   (1)       3-(3-methoxyanilino)-5,5-                                                                         10 mg.                                                    dimethyl-2-(N-methyl-N-                                                       phenethylamino)methyl-2-                                                      cyclohexen-1-one hydrochloride                                      (2)       lactose             102 mg.                                         (3)       microcrystalline cellulose                                                                        70 mg.                                          (4)       magnesium stearate  8 mg.                                                                         190 mg.                                                                       per capsule                                     ______________________________________                                    

(1), (2), (3) and half quantity of (4) are throughly mixed, and then themixture is granulated. Remaining half of (4) is added to the granulesand the whole is filled into a gelatin capsule.

    ______________________________________                                        C.(Injection)                                                                 (1)        3-(3-methoxyanilino)-5,5-                                                                         5 mg.                                                     dimethyl-2-(N-methyl-N-                                                       phenethylamino)methyl-2-                                                      cyclohexen-1-one hydrochloride                                     (2)        inositol            100 mg.                                        (3)        benzyl alcohol      20 mg.                                         ______________________________________                                    

All ingredients are dissolved in water to make 2.0 ml of the solution(pH 7.5) serving as injection.

Reference Example 1

16.2 Parts of a 37 % aqueous solution of formaldehyde is cooled wellwith a refrigerating agent, and while the internal temperature ismaintained at a temperature not exceeding 5°C, 14.6 parts ofdiethylamine is added dropwise, with stirring. At temperatures notexceeding 5°C, the whole mixture is stirred for 2 and a half hours.Then, anhydrous potassium carbonate is added to the resulting reactionmixture so as to cause produced diethylaminomethanol to separate. Theseparated oil are collected and dried over anhydrous potassiumcarbonate, whereby a colorless, clear solution of diethylaminomethanolis obtained. The resulting compound is identified by the data ofmagnetic nuclear resonance spectrum and infrared absorption spectrum.

What we claim is:
 1. A member selected from the group consisting of acompound of the formula ##SPC4##wherein each of R¹ and R² independentlyrepresents hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; one of R³and R⁴ represents hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2to 6 carbon atoms, or cycloalkyl of up to 6 carbon atoms, and the otherrepresents (a) phenyl, (b) phenyl substituted by a member of the groupconsisting of alkyl of 1 to 3 carbon atoms, hydroxyalkyl of 1 to 3carbon atoms, alkoxy of 1 to 3 carbon atoms, halogen, nitro, hydroxy,mono- or di-alkylamino wherein the alkyl is of 1 to 2 carbon atoms, (c)alkyl of 1 to 6 carbon atoms, (d) alkenyl of 2 to 6 carbon atoms, (e)cycloalkyl of up to 6 carbon atoms, (f) benzyl or (g) phenethyl; one ofR⁵ and R⁶ represents hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of2 to 6 carbon atoms or cycloalkyl of up to 6 carbon atoms, and the otherrepresents alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms,cycloalkyl of up to 6 carbon atoms, phenyl, benzyl or phenethyl, and apharmaceutically acceptable salt thereof.
 2. A compound as claimed inclaim 1 wherein R¹ and R² are hydrogen.
 3. A compound as claimed inclaim 1 wherein R¹ and R² are alkyl of 1 to 6 carbon atoms.
 4. Acompound as claimed in claim 1 wherein R¹ and R² are alkyl of 1 to 4carbon atoms.
 5. A compound as claimed in claim 1 wherein R¹ and R² aremethyl.
 6. A compound as claimed in claim 1 wherein one of R¹ and R² isalkyl of 1 to 6 carbon atoms and the other is hydrogen.
 7. A compound asclaimed in claim 1 wherein one of R¹ and R² is hydrogen and the other isphenyl.
 8. A compound as claimed in claim 1 wherein one of R¹ and R² isalkyl of 1 to 6 carbon atoms and the other is phenyl.
 9. A compound asclaimed in claim 1 wherein R¹ and R² are phenyl.
 10. A compound asclaimed in claim 1 wherein one of R³ and R⁴ is hydrogen and the other isphenyl substituted by a member of the group consisting of alkyl of 1 to3 carbon atoms, hydroxyalkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3carbon atoms, halogen, nitro, hydroxy, mono- or di-alkyl amino whereinthe alkyl is of 1 to 2 carbon atoms.
 11. A compound as claimed in claim1 wherein one of R³ and R⁴ is hydrogen and the other is alkyl of 1 to 6carbon atoms.
 12. A compound as claimed in claim 1 wherein one of R³ andR⁴ is hydrogen and the other is benzyl or phenethyl.
 13. A compound asclaimed in claim 1 wherein one of R³ and R⁴ is alkyl of 1 to 6 carbonatoms and the other is phenyl.
 14. A compound as claimed in claim 1wherein R⁵ and R⁶ are alkyl of 1 to 6 carbon atoms.
 15. A compound asclaimed in claim 1 wherein one of R⁵ and R⁶ is alkyl of 1 to 6 carbonatoms and the other is phenyl.
 16. A compound as claimed in claim 1wherein one of R⁵ and R⁶ is alkyl of 1 to 6 carbon atoms and the otheris benzyl or phenethyl.
 17. A compound as claimed in claim 1 wherein oneof R⁵ and R⁶ is hydrogen and the other is benzyl or phenethyl.
 18. Acompound as claimed in claim 1 wherein one of R⁵ and R⁶ is hydrogen andthe other is phenyl.
 19. A compound as claimed in claim 1 wherein one ofR⁵ and R⁶ is hydrogen and the other is alkyl of 1 to 6 carbon atoms. 20.A compound as claimed in claim 1 wherein the compound is3-(3-chloroanilino)-5,5-dimethyl-2-dimethylaminomethyl-2-cyclohexen-1-one.21. A compound as claimed in claim 1 wherein the compound is3-(3-chloroanilino)-5,5-dimethyl-2-(N-methyl-N-phenethyl-amino)methyl-2-cyclohexen-1-one.22. A compound as claimed in claim 1 wherein the compound is3-(3-methoxyanilino)-5,5-dimethyl-2-dimethylaminomethyl-2-cyclohexen-1-one23. A compound as claimed in claim 1 wherein the compound is3-(3-methoxyanilino)-5,5-dimethyl-2-diethylaminomethyl-2-cyclohexen-1-one.24. A compound as claimed in claim 1, wherein the compound is3-(3-methoxyanilino)-5,5-dimethyl-2-(N-methyl-N-benzyl-amino)methyl-2-cyclohexen-1-one.25. A compound as claimed in claim 1, wherein the compound is3-(3-methoxyanilino)-5,5-dimethyl-2-(N-methyl-N-phenethylamino)methyl-2-cyclohexen-1-one.26. A compound as claimed in claim 1, wherein the compound is3-(4-ethoxyanilino)-2-(N-methyl-N-benzylamino)methyl-2-cyclohexen-1-one.27. A compound as claimed in claim 1, wherein the compound is3-(4-ethoxyanilino)-2-(N-methyl-N-phenethylamino)-methyl-2-cyclohexen-1-one.